Method and device for detecting a neural response in neural measurements

ABSTRACT

A method is provided for processing a neural measurement obtained in the presence of noise, in order to detect whether a locally evoked neural response is present in the neural measurement. A first neural measurement is obtained from a first sense electrode. A second neural measurement is contemporaneously obtained from a second sense electrode spaced apart from the first electrode along a neural pathway of the neural response. A neural response decay is determined, being a measure of the decay in the neural response from the first sense electrode to the second sense electrode. A ratio of the neural response decay to an amplitude normalising term is calculated. From the ratio it is determined whether a locally evoked neural response is present in the neural measurement.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national stage of Application No.PCT/AU2015/050724, filed Nov. 17, 2015, which application claims thebenefit of Australian Provisional Patent Application No. 2014904595,filed Nov. 17, 2014, the disclosures of which are incorporated herein byreference in their entireties.

TECHNICAL FIELD

The present invention relates to detection of a neural response, such asa neural response caused by a stimulus. In particular the presentinvention relates to detection of a compound action potential by usingone or more electrodes implanted proximal to the neural pathway toobtain a neural measurement.

BACKGROUND OF THE INVENTION

Electrical neuromodulation is used or envisaged for use to treat avariety of disorders including chronic pain, Parkinson's disease, andmigraine, and to restore function including but not limited to hearingand motor function. A neuromodulation system applies an electrical pulseto neural tissue in order to generate a therapeutic effect. Such asystem typically comprises an implanted electrical pulse generator, anda power source such as a battery that may be rechargeable bytranscutaneous inductive transfer. An electrode array is connected tothe pulse generator, and is positioned close to the neural pathway(s) ofinterest. A suitable electrical pulse applied to the neural pathway byan electrode causes the depolarisation of neurons, which generatespropagating action potentials whether antidromic, orthodromic, or both,to achieve the therapeutic effect.

When used to relieve chronic pain for example, the electrical pulse isapplied to the dorsal column (DC) of the spinal cord and the electrodearray is positioned in the dorsal epidural space. The dorsal columnfibres being stimulated in this way inhibit the transmission of painsignals through that segment in the spinal cord to the brain.

In general, the electrical stimulus generated in a neuromodulationsystem triggers a neural action potential which then has either aninhibitory or excitatory effect. Inhibitory effects can be used tomodulate an undesired process such as the transmission of pain, orexcitatory effects can be used to cause a desired effect such as thecontraction of a muscle or stimulation of the auditory nerve.

The action potentials generated among a large number of fibres sum toform a compound action potential (CAP). The CAP is the sum of responsesfrom a large number of single fibre action potentials. When a CAP iselectrically recorded, the measurement comprises the result of a largenumber of different fibres depolarising. The propagation velocity isdetermined largely by the fibre diameter and for large myelinated fibresas found in the dorsal root entry zone (DREZ) and nearby dorsal columnthe velocity can be over 60 ms⁻¹. The CAP generated from the firing of agroup of similar fibres is measured as a positive peak P1 in therecorded potential, then a negative peak N1, followed by a secondpositive peak P2. This is caused by the region of activation passing therecording electrode as the action potentials propagate along theindividual fibres, producing the typical three-peaked response profile.Depending on stimulus polarity and the sense electrode configuration,the measured profile of some CAPs may be of reversed polarity, with twonegative peaks and one positive peak.

To better understand the effects of neuromodulation and/or other neuralstimuli, and for example to provide a stimulator controlled by neuralresponse feedback, it is desirable to accurately detect a CAP resultingfrom the stimulus. Evoked responses are less difficult to detect whenthey appear later in time than the artifact, or when the signal-to-noiseratio is sufficiently high. The artifact is often restricted to a timeof 1-2 ms after the stimulus and so, provided the neural response isdetected after this time window, a response measurement can be moreeasily obtained. This is the case in surgical monitoring where there arelarge distances (e.g. more than 12 cm for nerves conducting at 60 ms⁻¹)between the stimulating and recording electrodes so that the propagationtime from the stimulus site to the recording electrodes exceeds 2 ms.

To characterize the responses from the dorsal columns, high stimulationcurrents and close proximity between electrodes are required, andtherefore in such situations the measurement process must overcomeartifact directly. However, this can be a difficult task as an observedCAP signal component in the neural measurement will typically have amaximum amplitude in the range of microvolts. In contrast a stimulusapplied to evoke the CAP is typically several volts and results inelectrode artifact, which manifests in the neural measurement as adecaying output of several millivolts partly or wholly contemporaneouslywith the CAP signal, presenting a significant obstacle to isolating oreven detecting the much smaller CAP signal of interest.

For example, to resolve a 10 uV CAP with 1 uV resolution in the presenceof an input 5 V stimulus requires an amplifier with a dynamic range of134 dB, which is impractical in implant systems. As the neural responsecan be contemporaneous with the stimulus and/or the stimulus artefact,CAP measurements present a difficult challenge of measurement amplifierdesign. In practice, many non-ideal aspects of a circuit lead toartefact, and as these mostly have a decaying exponential appearancethat can be of positive or negative polarity, their identification andelimination can be laborious.

The difficulty of this problem is further exacerbated when attempting toimplement CAP detection in an implanted device. Typical implants have apower budget which permits a limited number, for example in the hundredsor low thousands, of processor instructions per stimulus, in order tomaintain a desired battery lifetime. Accordingly, if a CAP detector foran implanted device is to be used regularly (e.g. once a second), thenthe detector should preferably consume only a small fraction of thepower budget and thus desirably should require only in the tens ofprocessor instructions in order to complete its task.

Approaches proposed for obtaining a neural measurement include thatdescribed in International Patent Publication No. WO 2012/155183.Approaches to identifying whether a neural response is present in aneural measurement include the propagram method described inInternational Patent Publication No. WO 2012/155190.

Any discussion of documents, acts, materials, devices, articles or thelike which has been included in the present specification is solely forthe purpose of providing a context for the present invention. It is notto be taken as an admission that any or all of these matters form partof the prior art base or were common general knowledge in the fieldrelevant to the present invention as it existed before the priority dateof each claim of this application.

Throughout this specification the word “comprise”, or variations such as“comprises” or “comprising”, will be understood to imply the inclusionof a stated element, integer or step, or group of elements, integers orsteps, but not the exclusion of any other element, integer or step, orgroup of elements, integers or steps.

In this specification, a statement that an element may be “at least oneof” a list of options is to be understood that the element may be anyone of the listed options, or may be any combination of two or more ofthe listed options.

SUMMARY OF THE INVENTION

According to a first aspect the present invention provides a method forprocessing a neural measurement obtained in the presence of noise, inorder to detect whether a locally evoked neural response is present inthe neural measurement, the method comprising:

obtaining a first neural measurement from a first sense electrode;

obtaining a contemporaneous second neural measurement from a secondsense electrode spaced apart from the first electrode along a neuralpathway of the neural response;

determining a neural response decay, being a measure of the decay in theneural response from the first sense electrode to the second senseelectrode;

calculating a ratio of the neural response decay to an amplitudenormalising term; and

determining from the ratio whether a locally evoked neural response ispresent in the neural measurement.

According to a second aspect the present invention provides animplantable device for processing a neural measurement obtained in thepresence of noise, in order to detect whether a locally evoked neuralresponse is present in the neural measurement, the device comprising:

measurement circuitry for obtaining a first neural measurement from afirst sense electrode, and for contemporaneously obtaining a secondneural response measurement from a second sense electrode spaced apartfrom the first electrode along a neural pathway of the neural response;and

a processor configured to determine a neural response decay, being ameasure of the decay in the neural response from the first senseelectrode to the second sense electrode; the processor furtherconfigured to calculate a ratio of the neural response decay to anamplitude normalising term; and the processor further configured todetermine from the ratio whether a locally evoked neural response ispresent in the neural measurement.

According to a third aspect the present invention provides anon-transitory computer readable medium for processing a neuralmeasurement obtained in the presence of noise, in order to detectwhether a locally evoked neural response is present in the neuralmeasurement, comprising instructions which, when executed by one or moreprocessors, causes performance of the following:

obtaining a first neural measurement from a first sense electrode;

obtaining a contemporaneous second neural measurement from a secondsense electrode spaced apart from the first electrode along a neuralpathway of the neural response;

determining a neural response decay, being a measure of the decay in theneural response from the first sense electrode to the second senseelectrode;

calculating a ratio of the neural response decay to an amplitudenormalising term; and

determining from the ratio whether a locally evoked neural response ispresent in the neural measurement.

The present invention recognises that a locally evoked neural response,being a neural response evoked at a site close to the sense electrodes,such as within 100 mm or less, will undergo a decay in the CAP signalamplitude as it propagates away from the stimulus site, due at least inpart to a spreading in time of the responses of individual fibres havingdiffering conduction velocity, and a change in depth of individualfibres within the spinal cord as the CAP propagates. This is in contrastto a distally evoked response, which will present a substantiallyconstant neural signal strength to both sense electrodes. Accordinglythe present invention provides a way to determine whether a sensedneural response has been locally evoked or distally evoked. Such acapability may thus be used for example to characterise the performanceof a local electrical stimulus regime, without corruption from noisesuch as coexisting neural responses occurring on the neural pathway dueto the subject's independent motor activity and/or sensory stimulation.Such distally evoked responses give rise to considerable neural activityand, without a means for distinguishing between locally evoked responsesand distally evoked responses, distally evoked response noise can leadto a conclusion that locally applied electrical stimuli are performingappropriately when in fact they are not.

The neural response decay may in some embodiments be determined bydetermining a first amplitude of the first neural measurement,determining a second amplitude of the second neural measurement, andcalculating a difference between the first amplitude and the secondamplitude. In such embodiments, the CAP amplitude may be determined inany suitable manner, for example in accordance with the teachings ofAustralian Provisional Patent Application No. 2013904519, the content ofwhich is incorporated herein by reference. Additionally oralternatively, the neural response decay may in some embodiments bedetermined by determining a first width of the first neural measurement,determining a second width of the second neural measurement, andcalculating a difference between the first width and second width. Stillfurther embodiments may determine the ratio as being a ratio of theamplitude (or energy, power of other strength measure) of the firstneural measurement to the amplitude (or energy, power of other strengthmeasure) of the second neural measurement.

The amplitude normalising term may in some embodiments of the inventioncomprise a sum of the first amplitude and second amplitude, a sum ofscalar or other variants of the first amplitude and second amplitude, ascalar or other variant of the first amplitude alone, or a scalar orother variant of the second amplitude alone. The present inventionrecognises that such normalisation of the difference value is animportant element of detecting neural responses because of thepropensity of spinal cord electrode arrays to move relative to thespinal cord and alter the electrode-to-fibre distance, and because ofthe impact of the electrode-to-fibre distance upon both (i) theamplitude of the response evoked by a given stimulus, and (ii) theamplitude of a neural measurement obtained from a given neural response.

The first and second amplitudes are preferably determined at a moment ofthe respective measurement corresponding to an expected occurrence of aneural response to be detected, as determined by reference to anelectrical stimulus timing and a distance from the stimulus site to therespective sense electrode.

In some embodiments the measurement is obtained in accordance with theteachings of International Patent Publication No. WO 2012/155183, by thepresent applicant.

In some embodiments the detector output is used in a closed loopfeedback circuit to control neuromodulation, for example in conjunctionwith the techniques of International Patent Publication No. WO2012/155188, by the present applicant, the content of which isincorporated herein by reference. Such embodiments may thus effectfeedback control of electrical stimuli with improved resistance tocorruption by the patient's independent motor activity and/or peripheralstimuli.

In some embodiments the method may be repeated in order to obtain aplurality of ratios resulting from repeated application of a givenstimulus. The plurality of ratios may then give a probabilisticindication of the neural response decay to improve the determination ofwhether a locally evoked response is present.

In some embodiments, the method may be performed repeatedly, regularlyor substantially continuously, in order to monitor changes in the ratiowhich occur over time, for example in response to postural changes ofthe subject, movement of the subject, peripheral stimuli experienced bythe subject, electrode lead movement, injury or disease affecting theneural pathway, or a change in efficacy of a therapy such as medication.

In some embodiments the method of the present invention may furthercomprise the step of detecting whether any neural activity is present.Such embodiments recognise that insufficiently suppressed stimulusartefact also decays with distance from the stimulus site and the ratiomay thus give a false positive indication that a locally evoked responseis present, when in fact only artefact is present. By providing aseparate step of detecting whether neural activity is present, suchembodiments may provide improve performance in embodiments in whichstimulus artefact is inadequately or not suppressed. Such embodimentsmay comprise a signal quality indicator configured to assess the neuralmeasurement(s) in order to determine whether a signal appears to be aCAP, and if not to exclude the measurement from further processing.

In some embodiments, a contemporaneous third or additional neuralmeasurement may be obtained from a third or additional senseelectrode(s) spaced apart from the first and second electrodes along aneural pathway of the neural response. Such embodiments may be used forthree or more point fitting of a decay coefficient of the observedresponse, for use as a determinant of whether an observed response hasbeen locally evoked.

BRIEF DESCRIPTION OF THE DRAWINGS

An example of the invention will now be described with reference to theaccompanying drawings, in which:

FIG. 1 illustrates an implantable device suitable for implementing thepresent invention;

FIG. 2 is a schematic of a feedback controller to effect stimuluscontrol in response to neural recruitment in accordance with oneembodiment of the present invention;

FIG. 3 illustrates the reduction in observed amplitude of an evokedneural response with increasing distance from the stimulus site;

FIG. 4a illustrates the amplitude of observed neural responses of afirst patient, FIG. 4b is a time series of histograms of neural responsedecay values (R values) derived from FIG. 4a , FIG. 4c illustrates asingle histogram of signal, and noise, respectively, from the samepatient and FIG. 4d illustrates the time series of the R histogramsobtained in the absence of any locally evoked signals;

FIG. 5a illustrates selection of the upper and lower boundaries of aninclusion criterion, and FIG. 5b illustrates for each width setting thepercentage of consecutive non-usable points;

FIG. 6a is a time series of histograms of R values for evoked responsesignals for a second patient, FIG. 6b is a time series of histograms forthe same patient in the presence of noise only, and FIG. 6c illustratesthe performance of differing inclusion criteria;

FIG. 7a is a time series of histograms of R values for evoked responsesignals of a third patient, FIG. 7b illustrates the histogram of Rvalues obtained in the presence of noise only for the same patient, andFIG. 7c illustrates the performance of differing inclusion criteria;

FIG. 8 illustrates rejection of neural measurements using the inclusioncriteria; and

FIG. 9a is a plot of neural amplitude response data from a fourthpatient, FIG. 9b is a plot of the R data obtained from FIG. 9a , andFIG. 9c is a plot of the R data obtained from noise during the sameperiod of time.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 illustrates an implantable device 100 suitable for implementingthe present invention. Device 100 comprises an implanted control unit110, which controls application of neural stimuli, and controls ameasurement process for obtaining a measurement of a neural responseevoked by the stimuli from each of a plurality of electrodes. Thecontrol unit 110 includes a processor and a storage memory (or otherstorage device(s), not shown) for carrying out the method of the presentembodiment of the invention. Device 100 further comprises an electrodearray 120 consisting of a linear array of electrodes 122, each of whichmay be selectively used as either the stimulus electrode or senseelectrode, or both.

FIG. 2 is a schematic of a feedback controller implemented by thecontrol unit 110, based on recruitment. An important component of suchfeedback control is a recruitment estimator 230, which performs thedifficult task of detecting whether an evoked neural response is presentin a neural measurement as a result of the electrical stimulus.

In this embodiment, electrical stimuli are delivered to the spinal cord202 by one or more stimulus electrodes denoted E1 in FIG. 2. A desireddegree of recruitment, A R_(desired), is input by the user or by asetting made by a clinician when fitting the device or by any othersuitable means for defining desired recruitment. R_(desired) isprocessed by a controller and selector and passed to a stimulusgenerator which generates a stimulus to be delivered to the neuraltissue by E1. As will be appreciated while only a single stimuluselectrode E1 is shown in FIG. 2, a bipolar, monopolar or tripolarstimulus may be applied in conjunction with other stimulus electrodes,not shown. At the stimulus site adjacent to E1 within the spinal cord202, a neural response is evoked by the stimulus.

The neural response evoked by the stimulus at E1 is a compound responsecomprising the individual responses evoked in a number of fibres, andtakes a form shown at 210. The evoked response 210 propagates along therecruited fibres within the spinal cord 202 away from the stimulus siteadjacent to E1, and in so doing the form or morphology of the compoundresponse alters or decays. Without intending to be limited by theory,the decay in the neural response as it travels is at least in part dueto a spreading of the compound response resulting from each recruitedfibre having a conduction velocity which differs from the conductionvelocity of other recruited fibres, and the variation in depth of therecruited fibres within the cord 202 at different positions along thecord. At a time t2 the compound response passes sense electrode E2 andis recorded as having an amplitude and duration indicated at 212, whichdiffers from the form of the response at 210 in that response 212 is ofreduced amplitude and greater width or duration. At a later time t3,after undergoing further spreading and decay, the compound responsepasses sense electrode E3 and is recorded as having an amplitude andduration indicated at 214. Observed response 214 is of lesser amplitudebut greater duration then observed response 212. Similarly, at a latertime t4, after undergoing further spreading and decay, the compoundresponse passes electrode E4 and is recorded as having a furtherdecreased amplitude and increased duration as indicated at 216.

It is to be appreciated that the form of each observed response, asshown at 210, 212, 214 and 216, is illustrative. The decay and spreadingobserved in any neural response will depend at least upon thecharacteristics of the fibre population actually recruited by thestimulus, the neurophysiology of the subject, and the distance of theelectrodes from the fibres.

In accordance with the present invention, electrodes E2 and E3 are usedto obtain a first measurement 212 and a second measurement 214 of theneural response evoked by the stimulus, via measurement circuitry 222,224 respectively. The evoked CAP measurements in this embodiment aremade by use of the neural response measurement techniques set out inInternational Patent Publication No. WO2012/155183, with two datachannels recording simultaneous data from the two electrodes E2 and E3.

Applying a filter with optimized frequency and delay on each channel, inaccordance with the teachings of Australian Provisional PatentApplication No. 2013904519, the amplitude of the signals on each channelare determined and denoted as a pair of measurements CH1, CH2. Suchamplitude measurement pairs are obtained repeatedly over time for eachapplied stimuli. For each pair of measurements, a normalized neuralresponse decay value R is determined as follows:

$R = \frac{{{CH}\; 1} - {{CH}\; 2}}{{{CH}\; 1} + {{CH}\; 2}}$

FIG. 3 illustrates the reduction in observed amplitude of an evokedneural response with increasing distance from the stimulus site. As canbe seen the absolute difference between adjacent electrode recordings islarger when closer to the stimulus site, hence the selection of E2 andE3 as sense electrodes in this embodiment, however other electrode pairssuch as E3 and E4 or E2 and E4 may be used in alternative embodiments ofthe present invention. Once sufficiently distant from the stimulus sitewhich depending on the patient may be around 100 mm from the stimulus,and as indicated at 302, the amplitude remains at a constant non-zerolevel due to the nature of neural propagation. Thus, if a neuralresponse is evoked at such a distance or further away from the senseelectrodes, the observed amplitudes will be equal at each electrode andthe value of R will be zero (assuming no noise), or randomly spread inthe presence of noise. On the other hand, when a neural response isevoked locally to and a constant distance from the sense electrodes E2and E3, as is the case during effective stimulation from E1, R will takea constant non-zero value in the absence of noise, or will bedistributed about that non-zero value in the presence of noise in amanner distinguishable from the values of R in the region 302.

FIG. 4a illustrates the amplitude of observed neural responses from apatient over a period of about 90 seconds. As can be seen, the feedbackvariable, being the response amplitude sensed by electrode E2, variesconsiderably over time for example with changes in user posture, motoractivity (movement), and peripheral sensory input. Similar data (notshown) is obtained simultaneously from a second electrode E3 spacedfurther away from the stimulus site E1 than the first electrode E2. Inaccordance with the present embodiment, during this time period E1repeatedly delivered a stimulus, and R was determined for everyiteration. A histogram was then built of the calculated values of Rwithin a 3 second interval. This is repeated in the next 3 secondinterval to build a further histogram, with many such histograms beingbuilt over an extended period to generate the data shown in FIG. 4b . Inthis case of a locally evoked response, a band 402 can be seen in FIG.4b , where most of the ratios (R values) lie. In the present embodimentsthe measurement circuitry 222, 224 have differing offsets so that thecurve of FIG. 3 is not followed, and in particular in the presentembodiments this results in the Ratio taking a negative value despitewhat might be expected from FIG. 3 if the measurements had no offset.However the present invention is advantageous in this regard as it isthe tightness or existence of a band which can be determined,irrespective of the position of the band, allowing such measurementoffsets to be retained for measurement optimisation. In cases where themeasurements have no offset, it can be deduced from FIG. 3 that Ri=0indicates CH_(1i)=CH_(2i), while Ri=1 indicates that CH_(1i)>>CH_(2i).In this embodiment the dominant value of Ri is around −0.55, as seen inFIG. 4b . This band is then deemed to define the range in which anamplitude measurement is considered valid for this patient, so that anobserved response which produces an R in this range, or multipleobserved responses which produce an averaged R in this range, is deemedto have been a locally evoked neural response and not a distally evokedneural response.

FIG. 4c also illustrates a histogram 406 of R which was obtained bymaking multiple measurements each at a time when no response was locallyevoked. Histogram 406 illustrates that when measuring random noise ordistally evoked neural signals, while they may occasionally produce an Rwithin the band 402 they will not be consistently within it.

FIG. 4d illustrates the time series of the R histograms 406 obtained inthe absence of any locally evoked signals. As can be seen in FIG. 4d ,even though it is not known whether the sense electrodes are sensingdistally evoked neural responses or merely noise, either situation isclearly differentiated from the tightly banded R data produced bylocally evoked responses as shown in FIG. 4b . This shows that noise(which could comprise ascending or descending neural signals of remoteorigin, i.e. originating at the periphery or at the brain or otherwiseoriginating more than a few centimeters away from the measurementelectrodes) is not correlated and any neural activity is notsynchronised to the stimulus. Thus the present invention provides ameans by which to differentiate between a locally evoked CAP (e.g evokedby application of an electrical stimulus from an adjacent electrode) anda distally originating CAP (e.g. a CAP evoked by brain activity, reflexactivity or peripheral sensory inputs).

This technique requires the clinician to calibrate the boundary of range402 or the like for each patient, by performing a feedback experiment todetermine the required band for that patient within which the device isaccurately measuring a locally evoked CAP and not a distally evokedresponse.

The selection of the upper and lower boundaries of range 402 was furtherinvestigated. FIG. 5a illustrates the data of FIG. 4b with a number ofcandidate ranges illustrated, as indicated at 502. The range 502 wascentred about the mean value of R, and the width of the range 502 wasvaried in increments of 0.05. FIG. 5b illustrates, for each widthsetting of range 502, the percentage of consecutive non-usable points,being those points for which it is determined that the amplitudecalculated is not due to an evoked CAP, which arise for that inclusioncriteria.

It is further noted that, given the variability from one patient to thenext in the implantation site, electrode to fibre distance, and otherparameters, the absolute and relative response amplitudes observed canvary considerably between patients. FIG. 4a shows a typical responseamplitude of around 100 μV, whereas FIG. 6a illustrates data from apatient for whom the typical response amplitude was around 1,300 μV.FIG. 6a shows that a patient for whom large response measurements (>100μV) are obtained, gives a sharper histogram and a narrower band 602, ascompared to the band 402 in FIG. 4b . However, the patient of FIG. 6aexhibited a slower decay of neural response between the two electrodes(E3 and E4 in this instance), so that the R values are located muchcloser to zero. As can be seen with reference to FIG. 6b , thedistributions of R values obtained in the presence of noise only can beeasily distinguished from the tightly clustered data of FIG. 6a . FIG.6c , illustrating the performance of differing inclusion criteria forrange 602, also illustrates the improved sharpness of the histogram forthe patient of FIG. 6 as compared to the patient of FIG. 4. This likelyindicates not only that the original signals were smaller, but also thata higher proportion of the amplitudes measured for the patient of FIG. 6contained neural signals.

FIG. 7a illustrates R data for a patient for whom the amplitude of themeasured responses to electrical stimuli were much smaller, only around30 μV. As can be seen, the smaller absolute amplitudes result in abroader histogram 702, which is nevertheless clearly distinguishablefrom the noise-only histograms shown in FIG. 7b . FIG. 7c , illustratingthe performance of differing inclusion criteria for range 702, alsoillustrates the wider spread of the histogram for the patient of FIG. 7as compared to the respective patients of FIGS. 4 and 6.

FIG. 7c indicates that an inclusion criteria of 0.2, spanning a range ofR values of −0.1 to −0.3, will return a false negative for about 15% ofresponse measurements. FIG. 8 illustrates rejection of neuralmeasurements using the inclusion criteria, by rejecting those whose Rvalues fall outside of the set band. In particular FIG. 8 is an extractof the neural response amplitudes returned from one of the electrodes,with the dotted trace indicating the original amplitude values, and thesolid trace indicating the output once those measurements deemed to befalse measurements by the inclusion criteria are excluded. As expected,about 15% of measurements are rejected with the inclusion criteria setto such values. This illustrates that even for a patient from whom verysmall (˜30 μV) response amplitudes are obtained, the method of thepresent embodiment is capable of identifying locally evoked neuralresponses with a useful degree of selectivity.

The effect of neural response amplitude upon the band of R values wasinvestigated. FIG. 9a is a plot of neural amplitude response dataobtained over a 600 second period, with the target value (desired neuralresponse amplitude) being stepped upwards progressively from about 100seconds to 600 seconds, and the observed neural response amplitude (thefeedback variable) rising similarly, albeit with typical variations fromnoise, posture, etc.

FIG. 9b is a plot of the R data obtained from the E3 and E4 electrodesduring the period portrayed in FIG. 9a . As can be seen, the effect ofincreasing the stimulus current and thereby increasing the neuralresponse amplitude is to increase the amplitude of the histogram, butthis makes no difference to the centre position (mean R value) of thehistogram. FIG. 9c illustrates noise data obtained during the sameperiod but at times between stimuli when a locally evoked response isnot expected to arise, illustrating that distally evoked responsescontinue to be distinguishable from a locally evoked response even withvarying stimulus amplitude.

The present embodiments assume that the energy/amplitude ratio of theCAP as it propagates across electrodes is consistently within a certainrange for each patient. However, alternative embodiments may takemeasures which allow for variations in the energy/amplitude ratio. Forexample, such alternative embodiments may implement a low resolutionsliding time window and histogram calculation to determine if the peakhas shifted.

The present embodiment also assumes that what the estimator 230 picks upis in fact a CAP most of the time. In alternative embodiments, where itis possible that a tight histogram of R values might be returned due tothe presence of a constant artefact on both channels rather than due tothe presence of a decaying neural response, a signal quality indicatormay be integrated in order to exclude measurement pairs which are not ofthe typical three lobed shape of a neural response, for example.

It will be appreciated by persons skilled in the art that numerousvariations and/or modifications may be made to the invention as shown inthe specific embodiments without departing from the spirit or scope ofthe invention as broadly described. The present embodiments are,therefore, to be considered in all respects as illustrative and notlimiting or restrictive.

The invention claimed is:
 1. A method for detecting locally evokedneural responses in neural measurements obtained in the presence ofnoise, the method comprising: obtaining a first neural measurement of aneural response from a first sense electrode; obtaining acontemporaneous second neural measurement of the neural response from asecond sense electrode spaced apart from the first electrode along aneural pathway of the neural response; determining a neural responsedecay, being a measure of a decay in the neural response from the firstsense electrode to the second sense electrode; calculating a ratio ofthe neural response decay to an amplitude normalising term; determiningfrom the ratio whether a locally evoked neural response is present inthe neural measurement; and applying neurostimulation in response topresence of the locally evoked neural response using a closed loopfeedback circuit.
 2. The method of claim 1 wherein the determinedpresence of the locally evoked neural response is used to characterizethe performance of a local electrical stimulus regime.
 3. The method ofclaim 1 wherein the neural response decay is determined by determining afirst amplitude of the first neural measurement, determining a secondamplitude of the second neural measurement, and calculating a differencebetween the first amplitude and the second amplitude.
 4. The method ofclaim 1 wherein the neural response decay is determined by determining afirst width of the first neural measurement, determining a second widthof the second neural measurement, and calculating a difference betweenthe first width and second width.
 5. The method of claim 1 wherein theratio is determined as being a ratio of the amplitude or strength of thefirst neural measurement to the amplitude or strength of the secondneural measurement.
 6. The method of claim 3 wherein the amplitudenormalising term comprises a sum of scalar variants of the firstamplitude and second amplitude.
 7. The method of claim 3 wherein thefirst amplitude is determined at a first moment of the respective firstmeasurement corresponding to an expected occurrence of the neuralresponse determined by reference to an electrical stimulus timing and adistance from a stimulus site of the electrical stimulus to the firstsense electrode, and wherein the second amplitude is determined at asecond moment of the respective second measurement corresponding to anexpected occurrence of the neural response determined by reference to anelectrical stimulus timing and a distance from the stimulus site of theelectrical stimulus to the second sense electrode.
 8. The method ofclaim 1 wherein the method is repeated in order to obtain a plurality ofratios resulting from repeated application of a given stimulus in orderto give a probabilistic indication of the neural response decay toimprove the determination of whether a locally evoked response ispresent.
 9. The method of claim 1 wherein the method is performedrepeatedly in order to monitor changes in the ratio which occur overtime.
 10. The method of claim 1 further comprising a step of using asignal quality indicator to detect whether any neural activity ispresent to avoid false positives.
 11. The method of claim 1 furthercomprising obtaining a contemporaneous third or additional neuralmeasurement from a third or additional sense electrode(s) spaced apartfrom the first and second electrodes along a neural pathway of theneural response.
 12. An implantable device for detecting locally evokedneural responses in neural measurements obtained in the presence ofnoise, the device comprising: measurement circuitry for obtaining afirst neural measurement of a neural response from a first senseelectrode, and for contemporaneously obtaining a second neural responsemeasurement of the neural response from a second sense electrode spacedapart from the first electrode along a neural pathway of the neuralresponse; a processor configured to determine a neural response decay,being a measure of decay in the neural response from the first senseelectrode to the second sense electrode; the processor furtherconfigured to calculate a ratio of the neural response decay to anamplitude normalising term; and the processor further configured todetermine from the ratio whether a locally evoked neural response ispresent in the neural measurement; and a closed loop feedback circuitconfigured to apply neurostimulation in response to the presence of thelocally evoked neural response.
 13. A non-transitory computer readablemedium for detecting locally evoked neural responses in neuralmeasurements obtained in the presence of noise, comprising instructionswhich, when executed by one or more processors, causes performance ofthe following: obtaining a first neural measurement of a neural responsefrom a first sense electrode; obtaining a contemporaneous second neuralmeasurement of the neural response from a second sense electrode spacedapart from the first electrode along a neural pathway of the neuralresponse; determining a neural response decay, being a measure of decayin the neural response from the first sense electrode to the secondsense electrode; calculating a ratio of the neural response decay to anamplitude normalising term; and determining from the ratio whether alocally evoked neural response is present in the neural measurement;applying neurostimulation in response to presence of the locally evokedneural response using a closed loop feedback circuit.
 14. Theimplantable device of claim 12, wherein the processor is configured todetermine the neural response decay by determining a first amplitude ofthe first neural measurement, determining a second amplitude of thesecond neural measurement, and calculating a difference between thefirst amplitude and the second amplitude.
 15. The implantable device ofclaim 14, wherein the processor is configured to calculate the amplitudenormalising term as a sum of scalar variants of the first amplitude andsecond amplitude.
 16. The implantable device of claim 12, wherein theprocessor is configured to determine the neural response decay bydetermining a first width of the first neural measurement, determining asecond width of the second neural measurement, and calculating adifference between the first width and second width.
 17. The implantabledevice of claim 12, wherein the processor is configured to determine theratio as being a ratio of the amplitude or strength of the first neuralmeasurement to the amplitude or strength of the second neuralmeasurement.
 18. The implantable device of claim 12, wherein theprocessor is configured to determine the first amplitude at a firstmoment of the first measurement corresponding to an expected occurrenceof the neural response to be detected, as determined by reference to anelectrical stimulus timing and a distance from a stimulus site of theelectrical stimulus to the first sense electrode, and wherein theprocessor is configured to determine the second amplitude at a secondmoment of the respective second measurement corresponding to an expectedoccurrence of the neural response determined by reference to anelectrical stimulus timing and a distance from the stimulus site of theelectrical stimulus to the second sense electrode.
 19. The implantabledevice of claim 12, wherein the processor is configured to repeatedlydetect whether a locally evoked neural response is present in the neuralmeasurement, in order to obtain a plurality of ratios resulting fromrepeated application of a given stimulus in order to give aprobabilistic indication of the neural response decay to improve thedetermination of whether a locally evoked response is present.
 20. Theimplantable device of claim 12, further comprising a signal qualityindicator to detect whether any neural activity is present to avoidfalse positives.